Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries.
BACKGROUND
The present study was performed to investigate the influence of extracellular magnesium on changes in contractile tone induced by endothelin-1, and on relaxations to bradykinin in isolated porcine ciliary arteries.


METHODS
Vessels were studied in a myograph system for measurement of isometric forces. Concentration-response curves (10(-10)-10(-7) M) to endothelin-1 were constructed in the presence of different concentrations (0, 1.2, 2, 10 mM) of magnesium (MgSO4). Endothelin-1-precontracted vessels (approximately 10(-8) M) were exposed to magnesium (10(-5)-10(-2) M) in the presence or absence of either the inhibitor of nitric oxide formation L-NAME (approximately 10(-4) M), or different concentrations of calcium (2.5, 5, 10 mM). In endothelin-1-precontracted vessels (10(-8) M), relaxations to bradykinin (10(-10)-10(-6) M) were conducted in the presence of different concentrations of magnesium (0, 1.2, 10 mM).


RESULTS
Contractions to endothelin-1 were reduced only in the presence of 10 mM magnesium. (1.2 mM vs 10 mM, P = 0.001). In endothelin-1-precontracted vessels, magnesium evoked complete concentration-dependent relaxations (pD2 = 3.1 +/- 0.1), which were shifted to the right by increasing extracellular concentrations of calcium (2.5 vs 5 mM, P < 0.05). L-NAME had no influence on magnesium-induced relaxations. Relaxations to bradykinin remained unaffected by changes in extracellular magnesium concentrations.


CONCLUSIONS
In a mechanism which appears to be compatible with a calcium-antagonist effect, magnesium strongly modulates changes in contractile tone evoked by endothelin-1, but has no effect on bradykinin-induced relaxations.
Dettmann
E S
ES
Laboratory of Ocular Pharmacology and Physiology, University Eye Hospital Basel, Switzerland.
Lüscher
T F
TF
Flammer
J
J
Haefliger
I O
IO
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D019842:Ciliary Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009994:Osmolar Concentration; D013552:Swine
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D008274:Magnesium; D001920:Bradykinin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester